E-spatial

Many spatially resolved transcriptomic technologies do not have single-cell resolution but measure the average gene expression for each spot from a mixture of cells of potentially heterogeneous cell types. Here, we introduce a deconvolution method, conditional autoregressive-based deconvolution (CARD), that combines cell-type-specific expression information from single-cell RNA sequencing (scRNA-seq) with correlation in cell-type composition across tissue locations. Modeling spatial correlation allows us to borrow the cell-type composition information across locations, improving accuracy of deconvolution even with a mismatched scRNA-seq reference. **CARD** can also impute cell-type compositions and gene expression levels at unmeasured tissue locations to enable the construction of a refined spatial tissue map with a resolution arbitrarily higher than that measured in the original study and can perform deconvolution without an scRNA-seq reference. Applications to four datasets, including a pancreatic cancer dataset, identified multiple cell types and molecular markers with distinct spatial localization that define the progression, heterogeneity and compartmentalization of pancreatic cancer.

In this notebook, we present COMMOT (COMMunication analysis by Optimal Transport) to infer cell-cell communication (CCC) in spatial transcriptomic, a package that infers CCC by simultaneously considering numerous ligand–receptor pairs for either spatial transcriptomic data or spatially annotated scRNA-seq data equipped with spatial distances between cells estimated from paired spatial imaging data. A collective optimal transport method is developed to handle complex molecular interactions and spatial constraints. Furthermore, we introduce downstream analysis tools to infer spatial signaling directionality and genes regulated by signaling using machine learning models.

Classification of tumor and normal cells in the tumor microenvironment from scRNA-seq data is an ongoing challenge in human cancer study. Copy number karyotyping of aneuploid tumors (***copyKAT***) (Gao, Ruli, et al., 2021) is a method proposed for identifying copy number variations in single-cell transcriptomics data. It is used to predict aneuploid tumor cells and delineate the clonal substructure of different subpopulations that coexist within the tumor mass. In this notebook, we will illustrate a basic workflow of CopyKAT based on the tutorial provided on CopyKAT's repository. We will use a dataset of triple negative cancer tumors sequenced by 10X Chromium 3'-scRNAseq (GSM4476486) as an example. The dataset contains 20,990 features across 1,097 cells. We have modified the notebook to demonstrate how the tool works on BioTuring's platform.

Charting an organs’ biological atlas requires us to spatially resolve the entire single-cell transcriptome, and to relate such cellular features to the anatomical scale. Single-cell and single-nucleus RNA-seq (sc/snRNA-seq) can profile cells comprehensively, but lose spatial information. Spatial transcriptomics allows for spatial measurements, but at lower resolution and with limited sensitivity. Targeted in situ technologies solve both issues, but are limited in gene throughput. To overcome these limitations we present Tangram, a method that aligns sc/snRNA-seq data to various forms of spatial data collected from the same region, including MERFISH, STARmap, smFISH, Spatial Transcriptomics (Visium) and histological images. **Tangram** can map any type of sc/snRNA-seq data, including multimodal data such as those from SHARE-seq, which we used to reveal spatial patterns of chromatin accessibility. We demonstrate Tangram on healthy mouse brain tissue, by reconstructing a genome-wide anatomically integrated spatial map at single-cell resolution of the visual and somatomotor areas.